This proposal focuses on the interplay of tissue forces and surface forces arising at the air-liquid interface in the lung, and how these determine the microstructural environment leading to normal function or dysfunction of parenchymal mechanics, gas exchange, pulmonary capillary mechanics, and surfactant replacement therapy. These questions are especially important in establishing the fundamental mechanisms underlying the pathophysiologic differences in respiratory distress of newborns and adults, and why these differences lead to strikingly different efficacy of surfactant replacement therapy. Pulmonary capillary compliance is important to blood flow distribution in the lung, and to the transit and sequestration of leukocytes, a ubiquitous component of inflammation. Experiments will be done in anesthetized sheep and in excised lungs with surface tension alterations caused by saline lavage, rinses with constant surface tension oils, and oleic acid administration in vivo. The results will establish the manner in which acute lung injury influences: the geometry of alveoli and alveolar ducts, parenchymal stability, regional inhomogeneities resulting in poor gas exchange, and capillary mechanics. This proposal utilizes the novel technology of diffuse light scattering (DLS), wherein changes in pulmonary surface to volume ratio, capillary blood volume, and capillary oxygenation can be assessed. DLS is unique insofar as it can be applied in vivo and in unfixed excised preparations; it is a "window" on pulmonary mechanics and gas exchange heretofore unavailable for studies in both health and disease.